The objective of this investigation is to identify mechanisms responsible for differences in disease severity among patients with bronchial asthma. The investigations will be directed at five specific areas of concern: 1) The importance of beta-adrenergic blockade will be determined by performing beta-adrenergic receptor-binding studies in lymphocytes of patients using labeled dihydroalprenolol. Preliminary studies indicate decrease binding in asthmatic patients; 2) Airway hyperreactivity will be studied by measuring changes in pulmonary function following inhalation of increasing concentrations of aerosolized methacholine. Our preliminary studies suggest a relationship between the clinical complaints suggesting hyperreactive airway and actual physiologic measurements; 3) The role of allergic and immunologic factors will be determine by detailed immunologic and allergic history, skin testing and allergic history, skin testing and measurement of total IgE and specific IgE; 4) Platelet aggregation studies may identify subgroups of asthmatics. Preliminary data suggests asthma on an immunologic basis can be differentiated from nonimmunologic asthma; 5) Urinary excretory patterns of catecholamines will be measured. Our preliminary data suggests that those subjects with the most severe disease have greater norepinephrine excretion. While the mechanisms underlying observed variations in disease severity and response to treatment are not known, the present investigation addresses itself to this basic area of concern. Identifying which mechanisms influence clinical and physiologic severity of asthma would hopefully lead to a more rational and effective approach to therapy.